Do no harm guiding principle for physicians. Historical concern unsafe drugs on the market. Thalidomide (1950s) for morning sickness; caused birth defect in some children whose mothers took the drug during pregnancy. Drug manufacturers are now required to prove, scientifically, that the drug is safe and effective. Adequate information about pharmacological/toxicological studies on lab animals or in vitro. The kind, duration and scope of animal and other tests varies. Guidance documents are available (from the fda on how to meet these requirements) Generally in two species (1 rodent, 1 non-rodent) drug may behave differently in different species & not always clear which species is more predictive for humans. Identifying & characterizing dose-limiting toxicity of lead compound before clinical trials. Exaggerate the dosing and duration of exposure relative to intended clinical use. Chronic exposure studies in animal models (6-12 months) Surrogate measures of organ toxicity by measuring the blood or urine. Ld50 dose to kill 50% of cellular/organism population.